DESCRIPTION: This project will use functional magnetic resonance imaging to examine the nature and organization of memory operations in the prefrontal cortex (PFC) and medial temporal lobe (MTL) of the human brain. Although traditionally PFC has been associated with working memory and MTL with episodic memory, recent neuroimaging studies suggest that this distinction may not fully capture the relations across these different forms of memory. This proposal will examine the involvement of PFC and MTL in working memory and later episodic memory formation, specifically exploring the nature of the mnemonic processes mediated by distinct sub-regions within PFC and MTL. It is hypothesized that a process-based organization is present in both PFC and MTL such that the maintenance of information will be neurally dissociable from the manipulation of and integration across items. Experiment 1 will examine whether there is a similar process basis for the recruitment of PFC and MTL, using event-related functional magnetic resonance imaging (fMRI) analyses to identify regions that predict later item-based and relational memory. Experiment 2 will investigate the nature of ventrolateral and dorsolateral PFC operations by exploring how interference modulates PFC activation. Experiments 3-4 will examine if process-specific activation in PFC and MTL generalizes across learning and test contexts by distinguishing between regions that are associated with memory for an item and those associated with memory for the association between an item and its context and/or source. These studies should serve to elucidate the nature of and commonalities between PFC and MTL mnemonic processes, furthering our understanding of these critical structures that are susceptible in Alzheimer?s and Parkinson?s disease, Schizophrenia, and healthy aging.